Rescue of ATPa3-deficient murine malignant osteopetrosis by hematopoietic stem cell transplantation in utero
| العنوان: | Rescue of ATPa3-deficient murine malignant osteopetrosis by hematopoietic stem cell transplantation in utero |
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| المؤلفون: | Maria Grazia Bruzzone, Cristina Sobacchi, Roberto Colombo, Anna Villa, Maria Cristina Magli, Francesco Cerisoli, Antonio Musio, Maria Grazia Sacco, Sara E. Kalla, Allison C. Sharrow, Harry C. Blair, Enrica Mira Catò, Annalisa Frattini, Paolo Vezzoni, Francesca Faggioli, Alessandra Pangrazio, Francesca Rucci |
| المصدر: | Proceedings of the National Academy of Sciences. 102:14629-14634 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Genetically modified mouse, Vacuolar Proton-Translocating ATPases, medicine.medical_treatment, Green Fluorescent Proteins, Bone Matrix, Osteoclasts, Heterologous, Enzyme-Linked Immunosorbent Assay, Mice, Transgenic, Hematopoietic stem cell transplantation, Biology, Mice, Pregnancy, medicine, Animals, Fetal Therapies, Multidisciplinary, Cartilage, Hematopoietic Stem Cell Transplantation, Hematopoietic stem cell, Biological Sciences, Phenotype, Radiography, medicine.anatomical_structure, In utero, Osteopetrosis, Immunology, Cancer research, Female, Bone marrow |
| الوصف: | Autosomal recessive osteopetrosis (ARO) is a paradigm for genetic diseases that cause severe, often irreversible, defects before birth. In ARO, osteoclasts cannot remove mineralized cartilage, bone marrow is severely reduced, and bone cannot be remodeled for growth. More than 50% of the patients show defects in the osteoclastic vacuolar-proton-pump subunit, ATP6a3. We treated ATP6a3-deficient mice by in utero heterologous hematopoietic stem cell (HSC) transplant from outbred GFP transgenic mice. Dramatic phenotype rescue by GFP osteoclasts was obtained with engraftment, which was observed in most cases. Engraftment survived for variable periods. Recipients were not immunosuppressed, and graft-versus-host disease was not observed in all pups born after in utero treatment. Thus, differentiation of unmatched HSC transplanted in utero is sufficient to prevent fatal defects in ARO and may prevent complications of ARO unresponsive to conventional bone marrow transplantation. The presence of defective cells is not a barrier to the rescue of the phenotype by donor HSC. |
| تدمد: | 1091-6490 0027-8424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::21043632924e2f576a58a7e65995aa36 https://doi.org/10.1073/pnas.0507637102 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....21043632924e2f576a58a7e65995aa36 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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